Robust designs involving partial triallel crosses for breeding experiments

Obtaining information regarding general combining ability (Gca) and specific combining ability (sca) effects can be the major objective of a breeding programme to release new hybrids with enhanced genetic potential. This study included designs involving partial triallel crosses as they, being genetically more viable and consistent performers, involve lesser number of crosses leading to a lower degree of fractionation. An optimal or efficient design for triallel cross experiment may become disconnected and inefficient if the underlying assumptions are not fulfilled due to a missing observation pertaining to a cross. The robustness of designs against missing observation using connectedness and efficiency criteria has been studied both under unblocked and blocked situations. A list of efficient robust designs for triallel cross experiments has been tabulated for both unblocked and blocked situation. Programs have been written in SAS [PROC IML] software for computing efficiency factor of the designs involving triallel crosses for estimating Gca effects to investigate the robustness of designs against missing observation by calculating the efficiency factor

A General Bayesian Approach to Analyzing Diallel Crosses of Inbred Strains

The classic diallel takes a set of parents and produces offspring from all possible mating pairs. Phenotype values among the offspring can then be related back to their respective parentage. When the parents are diploid, sexed, and inbred, the diallel can characterize aggregate effects of genetic background on a phenotype, revealing effects of strain dosage, heterosis, parent of origin, epistasis, and sex-specific versions thereof. However, its analysis is traditionally intricate, unforgiving of unplanned missing information, and highly sensitive to imbalance, making the diallel unapproachable to many geneticists. Nonetheless, imbalanced and incomplete diallels arise frequently, albeit unintentionally, as by-products of larger-scale experiments that collect F1 data, for example, pilot studies or multiparent breeding efforts such as the Collaborative Cross or the Arabidopsis MAGIC lines. We present a general Bayesian model for analyzing diallel data on dioecious diploid inbred strains that cleanly decomposes the observed patterns of variation into biologically intuitive components, simultaneously models and accommodates outliers, and provides shrinkage estimates of effects that automatically incorporate uncertainty due to imbalance, missing data, and small sample size. We further present a model selection procedure for weighing evidence for or against the inclusion of those components in a predictive model. We evaluate our method through simulation and apply it to incomplete diallel data on the founders and F1's of the Collaborative Cross, robustly characterizing the genetic architecture of 48 phenotypes

SPECIAL TOPICS FOR RECOMBINANT INBRED INTERCROSS DATA: MODEL IDENTIFIABILITY, HYPOTHESIS TESTING AND COMPOSITIONAL METHODS

This dissertation addresses statistical issues in studies comprised of mice derived from the Collaborative Cross (CC) project (Churchill, 2004). Briefly, the CC is a community effort to derive novel inbred mouse strains from a genetically diverse set of eight inbred founder strains. Specifically, our interest has been in studying the effects of the parental strains on phenotypes of interest among recombinant intercrosses (RIX) derived from those strains (i.e., pairings of them). The topics explored here involve properly accounting for the relatedness of the samples created in these breeding schemes. When polygenic effects are conceptualized as uncorrelated parental strain effects, a study design can be framed as a sparse diallel, or more generally “dyadic” data. In Chapter 2, we consider such designs, incorporating multiple variance components. This raises often-ignored identifiability issues, the most significant of which is the possibility of performing inference on an unidentifiable model parameter - a mistake which is actually not difficult to make in this setting. We develop a formal an easy-to-apply condition to check for model identifiability in this setting. In Chapter 3, our focus is on hypothesis testing in these same sparse diallels. Because variance parameters are boundary parameters, inference is considered a “non-standard’’ problem, with asymptotic reference distributions being (sometimes complicated) mixtures of chi-squared random variables, when they are available at all. This is further complicated by the fact that when the dependent variable is non-normal, the data structure in this complicated setting does not allow for likelihood-based methods, as integration over the random effects becomes computationally infeasible. We adapt an existing score statistic developed by Lin (1997), which is designed for models fit by penalized quasi-likelihood. In Chapter 4, we directly model the relatedness of the strains by replacing the diallel-like random design matrices with ones derived from similarity matrices. Further, we incorporate the contributions of the eight founder strains as fixed effects, and propose a framework incorporating the statistic employed in Chapter 3 to jointly test the fixed and random genetic effects. We show that the benefits of this approach include improved power and more meaningful interpretations of parameter estimates.Doctor of Philosoph

Experimental Design & Analysis with Multiparental Populations

Multiparental populations (MPP) are experimental populations descended from more than two founder or parental inbred strains. They generally possess far greater genetic variation and phenotypic variability than simpler bi-parental populations, and are thus powerful resources for genetic studies,. MPP have been developed in numerous model systems, and have been successfully utilized in genetic association or quantitative trait locus (QTL) mapping studies for identifying candidate genes and variants that modulate complex phenotypes. Statistical methods developed for simpler populations have been extended successfully for analyses of MPP, though problems can arise, such as dubious QTL that occur at positions with imbalanced founder haplotype contributions. This shortcoming reflects the potential value of statistical tools designed specifically for MPP that can better leverage the abundant genetic and phenotypic variation for design and analyses of powerful experiments. This dissertation has two main topics: 1) experimental design and 2) genetic association and related analyses in MPP. Within the topic of experimental design, the use of the diallel, a specific form of MPP, to inform selection of powerful follow-up bi-parental crosses for QTL mapping is explored. More broadly, this approach represents a Bayesian decision theoretic approach and is found to provide a quantitative, principled procedure for leveraging information in the pilot data towards follow-up experiments. The second design subject is a power calculation tool for the Collaborative Cross (CC), a panel of recombinant inbred strains of mice, providing highly tailored power estimates for the design of mapping studies in the realized CC strains. Additionally, the tool is used to investigate how various aspects of experimental design and features of the underlying QTL affect the power to map QTL broadly. The first subject for the topic of genetic association is a multiple imputation approach to QTL mapping in MPP that is shown to reduce false QTL that result from founder haplotype uncertainty and imbalanced founder haplotype contributions. Next, an analysis of heterogeneous stock rats, an outbred MPP, is presented, in which imputed SNP association and fine-mapping approaches, including an integrative mediation procedure, are used to identify candidate variants influencing adiposity phenotypes. Finally, QTL mapping is performed on gene expression and chromatin accessibility outcomes in the CC, which largely detect local signals (within 5 Mb upstream or downstream of target outcome). These analyses are followed by a genome-wide integrative mediation approach, that detects local signatures of mediation of gene expression through chromatin accessibility, in a limited sample of CC mice.Doctor of Philosoph

En kvantitativ genetisk studie av andel hannfisk hos tilapia

Early sexual maturation is one the main constraints in Tilapia farming since early breeding causes stunted growth and large size variability. To circumvent this problem all-male populations are used commercially, and production of all male fry with use of hormones is the industry standard for Nile tilapia. To evaluate alternatives for production of all male fry, variation of male proportion of different strains and among strains combinations of Nile tilapia were studied. Additionally, to evaluate the feasibility of selection for increased male proportion, genetic parameters for male proportion were studied in Nile tilapia and hybrids between Nile and blue tilapias. None of the eight purebred Nile tilapia strain and strain crosses evaluated in Paper I showed a male proportion (MP) close to the desired commercial threshold (above 95% males). Additive genetic variation for male proportion was estimated within a synthetic population of Nile tilapia. Moderate to low heritabilities were obtained, but estimates may be biased upwards due to effects of the major genetic sex determination factors. Selection for increased male proportion will be very difficult to implement since it likely will result in an increased proportion of masculinized XX sires, which will counteract the response to selection. If selection is to be implemented, use of hormones will be needed to reproduce the population. Identification of genetic sex through the use of genetic markers could provide more reliable estimates of the genetic parameters for MP. Genetic variation was also estimated among hybrids of Nile tilapia females and blue tilapia males. Heritability estimates were moderate to high. Since only one generation of data was evaluated there can still be some level of confounding between the additive genetic effects and the other effects common to full-sibs due to shallow pedigrees. Crossbreeding (hybrid production) may be a good way to increase male proportion in places where cold winters affect production since hybrids between these two species show high male proportion and increased low temperature tolerance as compared to pure Nile tilapia. To make the Nile x blue tilapia hybrid of interest also in a tropical environment the growth of the blue tilapia must be improved through selection.Tidlig kjønnsmodning representerer en av de viktigste begrensningene i tilapiaoppdrett, siden tidlig reproduksjon medfører betydelig redusert vekst og stor variasjon i størrelse. For å omga dette problemet er kommersiell produksjon som regel basert på bruk av ”all male” populasjoner (dvs. kun hannfisk). I oppdrett av Nil tilapia (Oreochromis niloticus), som dominerer verdens tilapiaproduksjon, er kjønnsreversering av yngel ved hjelp av hormoner tilsatt i fôret i dag industristandarden. I dette arbeidet er alternative metoder for etablering av ”all male” populasjoner basert på utnyttelse av naturlig variasjon i andel hannfisk mellom ulike stammer og stammekombinasjoner vurdert. I tillegg er det estimert genetiske parametre for andel hannfisk hos Nil tilapia og hos hybrider mellom Nil tilapia og bla tilapia (O. aureus). Hos Nil tilapia undersøkt i et diallell krysningseksperiment gjennomført i GIFT prosjektet viste resultatene lave, men statistisk signifikante, additiv genetisk, heterosis og resiproke krysningseffekter for andel hannfisk. Av disse hadde de resiproke effektene størst betydning, og for å oppnå en økt andel av hanndyr bor derfor krysningene med høyest innslag av hanndyr benyttes. Basert på størrelsen på disse effektene synes det imidlertid klart at dette neppe vil vare tilstrekkelig til å oppnå minimum 95% hanndyr, noe som kreves for at denne strategien kan være et reelt alternativ til konvensjonelle metoder som i dag benyttes for produksjon av ”all male” populasjoner. Genetisk variasjon for andel hanndyr ble estimert i en syntetisk populasjon av Nil tilapia. Den beregnede arvegraden for egenskapen var lav til moderat, men estimatet kan likevel være overestimert på grunn av samspill med kjønnskromosomer. Seleksjon for økt andel hanndyr vil være svært krevende, fordi det, mest sannsynlig, vil resultere i en økt andel maskuliniserte XX fedre, noe som vil motvirke den ønskede seleksjonsresponsen i neste generasjon. Dersom seleksjon for økt andel hanndyr gjennomføres, vil bruk av hormoner være nødvendig for å få reprodusert populasjonen, og YY hanndyr og XY hunndyr kan dermed selekteres. Genetiske markører for kjønn eller avkomsgranskning av foreldre vil kunne øke effektiviteten av en slik seleksjonsstrategi. Genetisk variasjon for andel hanndyr ble også estimert for hybrider av Nil tilapia hunner og bla tilapia hanner. Arvegradsestimatene var moderate til høye. Siden det analyserte datasettet var begrenset til en enkelt årgang kan de additive genetiske effektene potensielt være sammenblandet med andre effekter felles for fullsøsken. På grunn av høyere toleranse for lave temperaturer hos bla tilapia kan slik hybridproduksjon være en god strategi i omrader der lave vintertemperaturer påvirker produksjonen. For at denne hybriden skal være kommersielt interessant i tropiske områder må tilveksten hos bla tilapia forbedres gjennom seleksjon.Akvaforsk Genetics Center (AFGC

Factors affecting residency rank-listing: A Maxdiff survey of graduating Canadian medical students

<p>Abstract</p> <p>Background</p> <p>In Canada, graduating medical students consider many factors, including geographic, social, and academic, when ranking residency programs through the Canadian Residency Matching Service (CaRMS). The relative significance of these factors is poorly studied in Canada. It is also unknown how students differentiate between their top program choices. This survey study addresses the influence of various factors on applicant decision making.</p> <p>Methods</p> <p>Graduating medical students from all six Ontario medical schools were invited to participate in an online survey available for three weeks prior to the CaRMS match day in 2010. Max-Diff discrete choice scaling, multiple choice, and drop-list style questions were employed. The Max-Diff data was analyzed using a scaled simple count method. Data for how students distinguish between top programs was analyzed as percentages. Comparisons were made between male and female applicants as well as between family medicine and specialist applicants; statistical significance was determined by the Mann-Whitney test.</p> <p>Results</p> <p>In total, 339 of 819 (41.4%) eligible students responded. The variety of clinical experiences and resident morale were weighed heavily in choosing a residency program; whereas financial incentives and parental leave attitudes had low influence. Major reasons that applicants selected their first choice program over their second choice included the distance to relatives and desirability of the city. Both genders had similar priorities when selecting programs. Family medicine applicants rated the variety of clinical experiences more importantly; whereas specialty applicants emphasized academic factors more.</p> <p>Conclusions</p> <p>Graduating medical students consider program characteristics such as the variety of clinical experiences and resident morale heavily in terms of overall priority. However, differentiation between their top two choice programs is often dependent on social/geographic factors. The results of this survey will contribute to a better understanding of the CaRMS decision making process for both junior medical students and residency program directors.</p

Genetic Combining Analysis of Food-Grade Maize: Colored and Quality Protein

Maize genetic diversity includes an array of kernel colors (red, blue, purple) with blue concentrated in the aleurone and red primarily in the pericarp. Quality protein maize (QPM) is improved over normal maize in regards to grain concentration of the essential amino acids lysine and tryptophan but has not been widely adapted in part due to lower than conventional yields. These are minimally-utilized specialty corns when compared to the yellows and whites commonly grown. Red, blue, and purple pigments are antioxidant phytochemicals produced by the plant as secondary metabolites. Antioxidants have been linked to anti-cancer and other anti-inflammatory health benefits. QPM hybrids are desirable in developing countries where subsistent agriculture is commonly practiced and quality protein cereals are non-existent. These two diverse maize categories have been the subject of little breeding research compared to normal maize and the potential for high phenolic content as well as the characterization of these QPM hybrids has not been previously investigated. We evaluated 153 maize hybrids (84 colored, 69 QPM) across three locations. High heritability estimates were found for phenolic content (0.80), tryptophan (0.46), and endosperm opacity (0.82). It was encouraging that all three traits observed little genotype by environment (GxE) interaction across diverse environments. This proved the trait analysis procedure to be robust in detecting and separating genotypes for both total phenolic content in colored maize, and amino acids in QPM. Top combiners for phenolics were the purple maize "maize morado" and red lines, with blue, yellow and white maize performing in descending order. Within the tested hybrids, high per kernel antioxidants (measured by total phenolics) may be the answer for producing the most total phenolics, with the top hybrid yielding greater than twice the total phenolics as the top yielding yellow hybrid. The top QPM hybrid out yielded the top normal hybrid by 35 and 30% for lysine and tryptophan. Additionally, QPM endosperm opacity primarily followed an additive, mid-parent trend, with some hybrids (20%) from diverse germplasm backgrounds deviating from that trend displaying the complexity and recessive nature of multiple modifier loci. Additional agronomic and composition traits were minimally correlated with phenolics

Exploration du phénomène d'heterosis chez deux espèces de levure d'oenologie : Saccharomyces cerevisiae et S. uvarum

Despite its biotechnological interest, heterosis has not commonly been studied or exploited in the yeast genus. This work aimed to explore this phenomenon within two yeast species well adapted to oenological conditions, Saccharomyces cerevisiae and S. uvarum. Eleven parental strains and their 55 intra- and inter-specific hybrids were phenotyped under enological conditions, at two temperatures in three replicates. A total of 396 alcoholic fermentations were characterized in depth through 35 phenotypic traits with original statistical and modeling tools. We first showed that, depending on the types of trait - kinetics parameters, life-history traits, enological parameters and aromas -, the sources of variation (strain, temperature and strain*temperature effects) differed in a large extent. Then we compared globally three groups of hybrids and their parents at two growth temperatures: intraspecific hybrids S. cerevisiae*S. cerevisiae, intraspecific hybrids S. uvarum*S. uvarum and interspecific hybrids S. cerevisiae*S. uvarum. We found that hybridization could generate multi-trait phenotypes with improved oenological performances and better homeostasis with respect to temperature. These results could explain why interspecific hybridization is so common in natural and domesticated yeast, and open the way to applications for wine-making.Malgré son potentiel, l’hétérosis a rarement été étudié, et encore moins exploité, chez les levures, espèces d’intérêt biotechnologique majeur. Ce travail avait pour objectif d’explorer ce phénomène chez deux espèces de levure, Saccharomyces cerevisiae et S. uvarum, dans des conditions proches de celles de l’œnologie. Pour la première fois des hybrides interspécifiques ont été inclus dans un dispositif diallèle complet. Un autre aspect original de ce travail résidait dans l’approche intégrative choisie, qui combinait l’étude de phénotypes aux niveaux métabolique, cellulaire et populationnel. Un panel de 66 souches (55 hybrides et leurs 11 parents) a été analysé pour 35 caractères à deux températures et avec trois réplicats, soit au total 396 fermentations alcooliques. Ces données nombreuses et complexes nous ont conduits non seulement à utiliser, mais aussi à développer divers outils statistiques et de modélisation originaux pour l’interprétation des données. Après avoir vérifié que les interactions nucléo-cytoplasmiques n’influençaient pas la variation des caractères étudiés, nous avons tout d’abord montré que les sources de variation (effet souche, effet température et interactions souche*température) différaient selon les types de caractères. Nous avons ensuite comparé globalement les trois groupes d’hybrides : intraspécifiques S. cerevisiae*S. cerevisiae, intraspécifiques S. uvarum*S. uvarum et interspécifiques S. cerevisiae*S. uvarum, et avons observé que l’hybridation interspécifique pouvait engendrer des phénotypes présentant de meilleures aptitudes œnologiques et une homéostasie supérieure à celle des hybrides intraspécifiques. Ce dernier résultat pourrait expliquer que l’hybridation interspécifique soit si fréquente chez les levures naturelles et domestiquées

Book of Abstracts - XIII EUCARPIA Biometrics in Plant Breeding Section Meeting - 30 August - 1 September 2006 - Zagreb, Croatia

The Book of Abstracts of the XIII EUCARPIA Biometrics in Plant Breeding Section Meeting held in 2006 in Zagreb, Croatia, contains the abstracts of 40 oral presentations and 22 posters as presented during six sessions: Linkage and LD based QTL Mapping Methodology I and II, Computer Science, Bioinformatics and Analysis of Large Data Sets, Crop Growth Modelling / Modelling GxE, and Collaborative Breeding. All the abstracts have been thoroughly reviewed by the members of Scientific Committee